Project Summary/Abstract DESCRIPTION: Lipids are essential cellular components and act as mediators in cell signaling. The function of lipids is determined by their structures. Dysregulated lipid metabolism is associated with a variety of pathological conditions, including Type 1 Diabetes (T1D). The levels of lipids cannot be predicted by the transcripts or proteins. To understand more about the role of lipids in the development of T1D, an important first step is to directly measure the temporal changes of lipids in an organism that shares similar physiology with human T1D. Built on our technological advancements in comprehensive global lipidomics, targeted lipidomic analysis of lipid mediators, isobaric labeling-based multiplexed analysis of intact glycolipids and determination of C=C unsaturation in intact lipids, in this project, we aim to profile the longitudinal changes of the nonobese diabetic (NOD) mouse lipidome during different stages of T1D development by accomplishing the following: 1) in-depth profile and accurately quantify the major lipids in T1D-pertinent tissues using global lipidomics; 2) use advanced technologies to improve structural resolution, accurately identify and quantify glycolipids and broadly profile bioactive lipid mediators; and 3) compare lipid expression profiles in different tissues and characterize lipidome remodeling during different stages of T1D development. Successfully accomplishing these goals will not only provide invaluable resource to the research community interested in the role of lipids in the development of T1D, but it will also provide better practices for conducting lipidomics research in general.